Ghrelin alleviates cancer chemotherapy-associated dyspepsia in rodents

Purpose: Chemotherapy treatment may lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Method: We examined the effects of ghrelin in rodent models of CADS induced by treatment with cisplatin. Results: In rats, increased gastric contents and reduced feeding were observed 48 h after injection with cisplatin (6 mg/kg, i.p.). Ghrelin (0.5 mg/kg, i.p.) caused a 16-fold increase in food intake over 1 h in cisplatin/ghrelin-treated rats compared to cisplatin/vehicle-treated rats. A single dose of ghrelin also restored the decreased locomotor activity in rats induced by cisplatin to almost the same level of saline-treated rats. In mice, daily food intake was significantly decreased at 24 h (60%) and 48 h (74%) after cisplatin (20 mg/kg, i.p.). Ghrelin (1 mg/kg, i.p.×2) significantly increased food intake measured at the 48 h time-point in both saline/ghrelin-treated and cisplatin/ghrelin-treated mice, with this effect being most marked in the cisplatin-treated group, where a twofold increase in feeding was observed. In cisplatin-treated mice, delayed gastric emptying was indicated by a 7.7-fold increase in the wet weight of gastric contents and ghrelin improved the gastric emptying index (GEI) by 31% (P<0.01). Conclusion: Together, these results suggest that it is possible to model cancer chemotherapy-induced dyspepsia in rodents and that ghrelin can greatly alleviate the behaviours associated with this syndrome. Agonists at the ghrelin receptor may, therefore, become a useful human therapeutic for this disorder.     

Ondansetron, metoclopramid, dexamethason, and their combinations compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: a prospective randomized study

Background A prospective randomized study was performed to assess the value of some individual risk factors for postoperative nausea and vomiting (PONV), and to compare the efficacy of ondansetron, metoclopramide, dexamethason, and combinations of these antiemetics in preventing PONV in patients after laparoscopic cholecystectomy. Methods The study enrolled 210 patients (157 women and 53 men) scheduled for laparoscopic cholecystectomy. The patients were randomly divided into seven groups. In groups 1 to 6, antiemetic drugs were administered. Group 7, the control group, received no antiemetic. For all the patients, individual risk factors for the incidence of nausea also were analyzed. Both nausea and vomiting were assessed separately 1, 4, 8, and 12 h after the procedure. Results Postoperative nausea and vomiting were significantly less frequent in menopausal women and more frequent in patients with a history of motion sickness. A comparison of mean values for the incidence of nausea and vomiting in groups 1 to 6 with the same values in group 7 showed that the mean PONV incidences were highest in groups 3 and 7, and the difference was significant. Conclusions Administration of antiemetic drugs significantly decreases the incidence of PONV in patients after laparoscopic cholecystectomy. The best decreases were achieved when ondansetron and dexamethason were applied together.     

Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism

Background: Patients receiving the highly emetogenic high-dose chemotherapy regimen with cyclophosphamide, thiotepa and carboplatin (CTC) may benefit from the neurokin-1 receptor antagonist aprepitant in addition to standard anti-emetic therapy. As aprepitant has been shown to be a moderate inhibitor of the cytochrome P450 (CYP) 3A4 isoenzyme, its effect on the pharmacokinetics and metabolism of cyclophosphamide and thiotepa was evaluated. Moreover, preliminary results on the clinical efficacy of aprepitant in the CTC regimen are reported. Patients and methods: Six patients were enrolled in a protocol that employed a 4-day course of CTC high-dose chemotherapy with cyclophosphamide (1,500 mg/m²/day), thiotepa (120 mg/m²/day) and carboplatin (AUC 5 mg min/ml/day). Two patients received the tCTC protocol, which comprises two-third of the dose of CTC. In addition to standard anti-emetic therapy, the patients received aprepitant from one day before the start of their course until 3 days after chemotherapy. Blood samples were collected on days one and three of the course and analyzed for cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide, thiotepa and its main active metabolite tepa. The influence of aprepitant on the pharmacokinetics of cyclophosphamide and thiotepa was analyzed using a population pharmacokinetic analysis including a reference population of 49 patients receiving the same chemotherapy regimen without aprepitant and sampled under the same conditions. The frequency of nausea and vomiting in the six patients receiving CTC was compared with those of the last 22 consecutive patients receiving CTC chemotherapy without aprepitant. Inhibitory activity of aprepitant on cyclophosphamide and thiotepa metabolism was also tested in human liver microsomes. Results: In our patient population, the rate of autoinduction of cyclophosphamide (P=0.040) and the formation clearance of tepa (P<0.001) were reduced with 23% and 33% when aprepitant was co-administered, respectively. Exposures to the active metabolite 4-hydroxycyclophosphamide and tepa were therefore reduced (5% and 20%, respectively) in the presence of aprepitant. In human liver microsomes, the 50% inhibitory concentrations (IC₅₀) of aprepitant for inhibition of cyclophosphamide (IC₅₀=1.3 g/ml) and thiotepa (IC₅₀=0.27 g/ml) metabolism were within the therapeutic range. Patients receiving aprepitant experienced less frequently CINV both during and after the CTC course compared with the reference population (nausea 3.7 days vs. 5.8 days, P=0.052; vomiting 0.5 days vs. 4.8 days, P<0.001). Conclusion: Aprepitant inhibited both cyclophosphamide and thiotepa metabolism, most probably due to inhibition of the CYP 3A4 and/or 2B6 isoenzymes. The effects of this interaction are, however, small compared to the total variability. Addition of aprepitant may provide superior protection against vomiting in patients receiving the highly emetogenic high-dose CTC chemotherapy.     

Assessment and management of gastrointestinal symptoms in advanced illness

Primary care clinicians increasingly encounter patients with advanced illness, many suffering from symptoms other than pain. Key principles that guide palliative care must be incorporated into a plan of care for each patient and family. Although medical management continues to be the mainstay of treatment, the generalist in palliative care needs to be familiar with the patient's preferences and goals of care. This article provides an overview of gastrointestinal symptoms including anorexia, cachexia, nausea, vomiting, and constipation. Advanced progressive illnesses are defined here as incurable conditions that have significant morbidity in the later stages of illness.     

Vomiting-Induced Pneumomediastinum and Subcutaneous Emphysema Does Not Always Indicate Boerhaave's Syndrome: Report of Six Cases

Spontaneous pneumomediastinum is an uncommon, self-limiting condition resulting from alveolar rupture in young adults. Because of the ambiguous presentation and the general lack of awareness of this condition, its diagnosis is often delayed, missed, or confused with spontaneous esophageal perforation. We report our experience of treating six patients who were referred to our unit with vomiting-induced pneumomediastinum, subcutaneous emphysema, and an initial diagnosis of spontaneous esophageal perforation. Ultimately, we diagnosed spontaneous pneumomediastinum in all six patients, who recovered uneventfully without any surgical intervention. We review the literature with particular emphasis on differentiating spontaneous pneumomediastinum from spontaneous esophageal perforation.     

恩丹西酮配合足三里穴位艾灸治疗顺铂所致迟发性呕吐的临床观察

目的观察恩丹西酮配合足三里穴位艾灸治疗顺铂（DDP）所致迟发性呕吐的临床效果。方法 100例患者随机分为治疗组和对照组各50例,治疗组给予恩丹西酮加入生理盐水于化疗前30min静脉滴注,第1～3天;艾灸足三里穴,第1～7天;对照组给予恩丹西酮加入生理盐水于化疗前30min静脉滴注,第1～3天。观察2组化疗后7d内呕吐情况。结果治疗组第3～7天治疗呕吐的总有效率高于对照组,差异有统计学意义（P〈0.05和P〈0.01）。结论恩丹西酮配合足三里穴位艾灸治疗DDP所致迟发性呕吐疗效好、经济、方便、安全,值得临床推广应用。     

托烷司琼预防腹腔镜胆囊切除术后恶心呕吐的疗效观察

目的观察托烷司琼预防腹腔镜胆囊切除术后恶心呕吐的疗效。方法选择ASAⅠ~Ⅱ级择期行腹腔镜胆囊切除术患者100例,随机分为托烷司琼组(T组)和对照组(N组),每组各50例,手术结束前10 min,T组静脉注射托烷司琼0.04 mg/kg,N组静脉注射0.9%生理盐水3 mL。观察并记录术后24 h内2组患者恶心呕吐的发生率。结果 T组恶心呕吐发生率明显低于N组(P<0.01)。结论托烷司琼可以显著降低腹腔镜胆囊切除术后患者24 h内恶心呕吐的发生率,有明显的预防效果。     

Chemotherapy-induced nausea and vomiting and antiemetic prophylaxis with palonosetron versus other 5-HT3 receptor antagonists in patients with cancer treated with low emetogenic chemotherapy in a hospital outpatient setting in the United States

Abstract

Background:

The incidence of overall (acute and delayed) chemotherapy-induced nausea and vomiting (CINV) events among patients treated with single- and multi-day low emetogenic chemotherapy (LEC) is not well established. We studied a cohort of patients receiving LEC and antiemetic prophylaxis with palonosetron (Group 1) versus other 5-HT₃ receptor antagonists (5-HT₃-RAs) (Group 2), to determine the overall rate of CINV and the proportion of patients experiencing delayed CINV (days 2–7 of a CT cycle) in a hospital outpatient setting.     

Acupoint Sticking at Shenque （CV 8） with Ginger-preparedBan Xia （Rhizoma Pinelliae） for Nausea and Vomiting Induced by Amifostine

Objective： To observe the treatment effect of acupoint sticking at Shenque （CV 8） with ginger-preparedBan Xia （Rhizoma Pinelliae） on nausea and vomiting induced by Amifostine for myelodysplastic syndromes （MDS）. Methods： Totally 124 eligible subjects intervened by Amifostine were randomized into 2 groups by the visiting order,an observation group and a control group,62 in each group. The control group was intervened by conventional treatment, while the observation group was by acupoint sticking at Shenque （CV 8） with ginger-preparedBan Xia （Rhizoma Pinelliae） in addition to the same conventional treatment. The occurrence rate of nausea and vomiting in the two groups were observed. Results： After intervention, the occurrence rate of nausea and vomiting in the observation group was significantly lower than that in the control group （P＆lt;0.01）. Conclusion： Acupoint sticking at Shenque （CV 8） with ginger-prepared Ban Xia （Rhizoma Pinelliae）can produce a content effect on nausea and vomiting induced by Amifostine for MDS.